The Veterinary Journal 216 (2016) 72–78

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The Veterinary Journal

j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / t v j l

Serum biochemistry profile, inflammatory cytokines, adipokines and

cardiovascular findings in obese dogs
Diego Piantedosi a, Antonio Di Loria b, Jacopo Guccione a,*, Angela De Rosa a, Silvia Fabbri a,
Laura Cortese a, Sergio Carta a, Paolo Ciaramella a
a Department of Veterinary Medicine and Animal Productions, University of Naples ‘Federico II’, via F. Delpino 1, 80137 Naples, Italy
b Department of Health Sciences, University Magna Græecia of Catanzaro, viale Europa-Germaneto, 88100 Catanzaro, Italy

A R T I C L E I N F O A B S T R A C T

Article history: The aim of this study was to evaluate the serum biochemistry profile, inflammatory cytokines, adipokines
Accepted 2 July 2016 and cardiovascular findings in obese dogs. Twenty obese and 20 normal weight healthy pet dogs were
recruited into the study, where they underwent blood testing and assessment of cardiovascular func-
Keywords: tion (blood pressure analysis, electrocardiography and echocardiography). Higher concentrations of total
Canine obesity cholesterol, triglycerides, lactate dehydrogenase, total serum proteins, α-globulins, total bilirubin, insulin,
Metabolic profile
insulin:glucose ratio, alkaline phosphate and alanine aminotransferase were observed in obese dogs than
Cytokine
dogs of normal weight. There were no differences in concentrations of tumour necrosis factor (TNF)-α
Adipokine
Cardiovascular or interleukin (IL)-6 between the two groups. Obese dogs had higher serum leptin but lower adiponectin
concentrations than dogs of normal weight. Systolic arterial blood pressure was higher in obese dogs
than dogs of normal weight. The values for the thickness of the free wall of the left ventricle and inter-
ventricular septal thickness were greater at end-diastole in obese dogs compared to dogs of normal weight.
Four of 20 obese dogs were determined to have obesity-related metabolic dysfunction (ORMD). The find-
ings indicate that a chronic inflammatory state is not necessarily evident in obese dogs, as has been described
in human beings, and the criteria used for ORMD can be used to define this syndrome in dogs. In this
study, canine obesity was associated with cardiac and vascular dysfunction.
© 2016 Elsevier Ltd. All rights reserved.

Introduction outcomes, including type 2 diabetes, cardiovascular disease and in-

Obesity is the most common nutritional disorder in the pet dog
population, whereby animals are considered to be clinically obese
when their body weight (BW) exceeds the optimum by at least 15%
(Laflamme, 2001). A high prevalence of canine obesity (25–52%) has
been reported in developed countries, where lifestyle, diet and lack
of exercise can contribute to dogs becoming overweight (Robertson,
2003; McGreevy et al., 2005; Colliard et al., 2006; Gossellin et al.,
2007).
Obesity is a metabolic disorder, representing an imbalance
between energy intake and energy expenditure. In human beings,
this is typically associated with the presence of low grade chronic
inflammation, characterised by dysregulation of a network of in-
flammatory signalling pathways, abnormal cytokine production and
increased concentrations of circulating acute phase proteins (Maury
and Brichard, 2010). This persistent inflammatory state, co-existing
with insulin resistance, is associated with a number of adverse
* Corresponding author.
E-mail address: jacopo.guccione@unina.it (J. Guccione).
creased susceptibility to neoplastic disease (Matarese et al., 2010).
Similar to the situation in humans, canine obesity can predis-
pose to or exacerbate several clinical conditions, such as osteoarthritis
and respiratory disease, as well as contribute to reduced longevi-
ty, increased surgical risk and exercise intolerance (Impellizeri et al.,
2000; Kealy et al., 2002; Bach et al., 2007). Although the relation-
ship between obesity and some of these conditions might be
explained by the mechanical/physical effects of the deposition of
excess fat tissue, associations with metabolic dysfunction, chronic
inflammation and cardiovascular disease are less clear in veteri-
nary medicine. Whereas German et al. (2009) described an increase
in insulin resistance in obese animals and a reduction of plasma in-
flammatory cytokines and adipokines following initiation of a weight
loss programme, Tvarijonaviciute et al. (2012a) reported that in-
flammatory biomarkers (such as acute phase proteins) remained
within the reference range in obese dogs before and after weight
loss. On the basis of a modification to the diagnostic criteria speci-
fied by the International Diabetes Federation, Tvarijonaviciute et al.
(2012b) classified around 20% of obese dogs with obesity-related
metabolic dysfunction (ORMD), with hyperinsulinaemia and reduced
concentrations of adiponectin. In a study of obese and lean dogs,
leptin, triglycerides and cholesterol were positively correlated with

http://dx.doi.org/10.1016/j.tvjl.2016.07.002
1090-0233/© 2016 Elsevier Ltd. All rights reserved.
 D. Piantedosi et al. / The Veterinary Journal 216 (2016) 72–78
body condition score (BCS), whilst a negative correlation was ob-
served for adiponectin and serotonin (Park et al., 2014).
There is limited published literature regarding the effects of
obesity on the cardiovascular system in dogs. Mehlman et al. (2013)
reported an increased systolic blood pressure and left ventricular
free wall thickness at end-diastole and end-systole in a small number
of obese dogs. In a retrospective study, hypertension was not related
to obesity in dogs (Pérez-Sánchez et al., 2015). The aim of the present
study was to evaluate the biochemical profile, inflammatory
cytokines and adipokines in the blood, as well as assessing cardio-
vascular parameters in obese dogs.
Materials and methods
Study population
Twenty obese (OB) and 20 normal weight (NW) healthy dogs were recruited into
the study from the client-owned referral population of the Veterinary Teaching Hos-
pital, Department of Veterinary Medicine and Animal Productions, University of Naples
‘Federico II’, Naples, from October 2014 to February 2015 (approved by the Ethical
Animal Care and Use Committee; date of approval: 26 June 2014). All dogs were of
mixed breed and medium size. Animals with evidence of pre-existing endocrine dis-
eases (e.g. diabetes mellitus, hypothyroidism, hyperadrenocorticism), hepatic and/
or renal failure, congenital or acquired cardiac diseases, inflammatory/infectious
diseases, systemic hypertension or pulmonary arterial hypertension, as well as phys-
iological conditions (e.g. pregnancy or lactation) were excluded from the study. A
nine-point body condition score (BCS) system (Laflamme, 1997) was employed and
scores were allocated by the same investigator. Dogs with a BCS ≥7/9 were consid-
ered to be obese (Tvarijonaviciute et al., 2012b). The dogs enrolled into the NW group
had a BCS of 5/9 and were considered to be healthy on the basis of clinical exam-
ination, complete blood count (CBC) and serum biochemistry.
Sample collection
Ten millilitres of blood were collected by jugular venepuncture after 12 h of fasting.
The first drops of blood were immediately taken for blood gas analysis, whilst the
remaining amount was divided into three fractions. The first fraction was placed in
tubes containing potassium ethylene diamine tetra-acetic acid (EDTA) for a CBC; the
second was placed in tubes without anticoagulant, allowed to clot and centrifuged
at 908 g for 15 min at 4 °C, while the third fraction was placed in tubes containing
lithium heparin anticoagulant and centrifuged at 327 g for 10 min at 4 °C. Serum
and plasma samples were stored at −80 °C and defrosted immediately before batch
analysis. Urine samples were collected by cystocentesis and stored at −80 °C until
analysis.
Complete blood count and serum biochemistry
CBCs were performed using a semi-automatic cell counter (Genius S, SEAC Radom
Group). Venous blood gas analysis, including pH, partial pressure of carbon dioxide
(pCO2), partial pressure of oxygen (pO2), base excess of the extracellular fluid (BEecf),
bicarbonate or alkaline reserve (HCO3), total content of carbon dioxide (TCO2) and
total oxygen saturation (SaO 2 ), was obtained using an automatic blood gas-
analyser (i-STAT, Abbott).
A semi-automatic chemical chemistry analyser (OLOT, Spinreact) was used to
analyse concentrations or activities of glucose, blood urea nitrogen (BUN), creati-
nine, triglycerides, total cholesterol, alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphate (ALP), total bilirubin (T-Bil), lactate de-
hydrogenase (LDH), sodium, potassium, albumin and total serum proteins (TP). Serum
protein electrophoresis was also performed. Plasma insulin measurements were
carried out in duplicate for each sample using a commercial ELISA kit (Canine insulin
ELISA, Mercodia AB), validated by Öberg et al. (2011). The insulin:glucose ratio (I:G)
was calculated as the plasma insulin (μU/mL) × 100/plasma glucose (mg/dL), ac-
cording to Bailhache et al. (2003). The urinary protein:creatinine ratio (UP:C) was
calculated after their spectrophotometric determination (OLOT, Spinreact).
Inflammatory cytokines and adipokines
Tumour necrosis factor (TNF)-α and interleukin (IL)-6 concentrations were mea-
sured in serum samples in duplicate using commercial canine cytokine ELISA kits
(Quantikine HS, R&D Systems) (Hofer et al., 2011; Paim et al., 2013; Park et al., 2015).
Serum adiponectin and leptin concentrations were measured in duplicate using com-
mercial canine ELISA kits (Millipore), validated by Tvarijonaviciute et al. (2010, 2011).
Systemic blood pressure
Five consecutive measurements of systemic arterial blood pressure were per-
formed using an automated oscillometric system (HDO, S + B MedVet) on the right
forelimb of conscious dogs, performed by the same operator. The highest and lowest
73
values of systolic, mean and diastolic arterial blood pressure were excluded, and the
mean of the remaining three measurements was recorded. Dogs with systolic ar-
terial blood pressure (SABP) >160 mmHg were considered to be hypertensive (Brown
et al., 2007).
Electrocardiography and echocardiography
A standard six-lead electrocardiogram (ECG model 08SD, BTL Italia) was per-
formed with dogs in right lateral recumbency. For each dog, a 2 min strip (paper
speed: 50 mm/s; calibration at 1 mV = 1 cm) was recorded. An echocardiographic
examination was undertaken for each dog, including transthoracic two-dimensional,
M-mode, spectral and colour flow Doppler (Mylab 50, Esaote). The echocardiographic
study was performed by the same investigator according to methodologies and ref-
erence ranges reported previously (Sahn et al., 1978; Bonagura, 1983; Thomas, 1984;
Shober and Fuentes, 2001; Hansson et al., 2002). For each measurement, mean values
derived from three consecutive cardiac cycles were considered. In the OB group, mono-
dimensional measurements of the left ventricle were compared with those of the
NW group and with the reference ranges, based on the actual weight in dogs
(Goncalves et al., 2002).
Criteria for obesity-related metabolic dysfunction (ORMD)
On the basis of the guidelines suggested by Tvarijonaviciute et al. (2012b), dogs
were considered to be affected by ORMD when BCS was ≥7/9 and at least two of
the following parameters were present: triglycerides >200 mg/dL, total cholesterol
>300 mg/dL, glucose >100 mg/dL and SABP >160 mmHg.
Statistical analysis
The data were assessed by the Shapiro–Wilk test to test for normality and where
necessary logarithmic transformation was performed to compare the OB and NW
groups using Student’s t test (SPSS version 20.0, IBM). P values < 0.05 were consid-
ered to be significant.
Results
The mean age, BW and BCS recorded in the OB group (four males,
two of which were spayed and 16 females, 15 of which were spayed)
were 8 ± 2.6 years, 20.8 ± 10.5 kg and 7.4 ± 0.7, respectively; com-
pared with 7.5 ± 0.5 years, 13.6 ± 6.4 kg and 5 ± 0, respectively for
the NW group (six entire males; 14 females, 10 of which were
spayed). The two groups showed a significant difference in BW
(P < 0.01). No significant difference for BW was seen with respect
to sex. In the OB group, 18 dogs were fed a mixed diet (commer-
cial and home-made food), while two dogs were fed a commercial
diet, with 17 dogs in this group also receiving snacks or treats; in
this group, 14 dogs had a BCS of 7, three had a BCS of 8 and three
had a BCS of 9. In the NW group, six dogs were fed a mixed diet,
13 were receiving a commercial diet and one dog a home-made diet.
Three NW dogs also received snacks or treats. The amount of daily
food was divided into two meals for the majority of dogs in both
groups.
The results of metabolic profiling of blood samples are
summarised in Table 1. The OB group had higher values than the
NW group for total cholesterol, triglycerides, LDH, TP and α2-
globulins (P < 0.01), as well as total bilirubin, insulin, I:G, ALP, ALT
and α1-globulins (P < 0.05). The values for ALT (5/20 dogs), ALP
(7/20 dogs), LDH (12/20 dogs) and T-Bil (2/20 dogs) were above the
upper limit of the reference range in the OB group. There were no
significant differences in haematological values, venous blood gas
results and UP:C values between groups.
There were no significant differences between groups in serum
TNF-α concentrations (mean ± SD: OB group 0.11 ± 0.01 pg/mL;
NW group 0.10 ± 0.01 pg/mL; Fig. 1A) or serum IL-6 concentra-
tions (mean ± SD: OB group 0.10 ± 0.12 pg/mL; NW group
0.08 ± 0.03 pg/mL; Fig. 1B). Serum TNF-α was undetectable in three
NW dogs, while IL-6 was below the limit of detection in three
OB dogs. Elevated serum leptin concentrations were significantly
higher in the OB group (12.19 ± 6.36 ng/mL) than the NW group
(5.80 ± 2.88 ng/mL; P < 0.01; Fig. 2A), whereas adiponectin values
74 D. Piantedosi et al. / The Veterinary Journal 216 (2016) 72–78

Table 1
Results of blood testing of samples from obese and normal weight dogs.

Parameter Unit Reference OB group NW group P value

range (n = 20) (n = 20)

Glucose mg/dL 65–118 80.1 ± 10.4 84.5 ± 11.8 0.223

Insulin μU/mL 5–20 11.0 ± 1.16 9.2 ± 1.8 0.011
I:G 13.9 ± 1.7 11.5 ± 3.3 0.045
BUN mg/dL 10–28 16.3 ± 10.0 18.1 ± 5.4 0.485
Creatinine mg/dL 0.5–1.5 1.2 ± 0.2 1.2 ± 0.2 0.709
T-Chol mg/dL 135–270 288.4 ± 117.4 201.4 ± 55.7 0.004
TG mg/dL 20–112 145.5 ± 64.1 66.5 ± 29.5 <0.001
ALT IU/L 21–102 141.0 ± 218.3 38.3 ± 13.9 0.042
AST IU/L 23–66 18.5 ± 13.6 18.8 ± 12.5 0.857
ALP IU/L 20–156 211.2 ± 236.3 73.6 ± 41.4 0.014
T-Bil mg/dL 0.1–0.5 0.6 ± 0.2 0.4 ± 0.0 0.010
LDH IU/L 45–233 383.9 ± 248.4 173.3 ± 42.5 <0.001
Na+ mmol/L 141–152 145.2 ± 2.8 145.7 ± 2.2 0.582
K+ mmol/L 4.37–5.35 4.0 ± 0.3 4.1 ± 0.3 0.376
TP g/dL 5.4–7.1 6.9 ± 0.4 6.1 ± 0.2 <0.001
Albumin g/dL 2.6–3.3 3.0 ± 0.3 2.8 ± 0.3 0.226
α1-globulin g/dL 0.2–0.5 0.41 ± 0.0 0.3 ± 0.0 0.023
α2-globulin g/dL 0.3–1.1 1.5 ± 0.3 1.0 ± 0.1 <0.001
β1-globulin g/dL 0.7–1.3 0.6 ± 0.2 0.5 ± 0.1 0.071
β2-globulin g/dL 0.6–1.4 0.7 ± 0.1 0.7 ± 0.1 0.490
γ-globulin g/dL 0.5–1.3 0.5 ± 0.2 0.5 ± 0.1 0.990

Reference ranges from Kaneko et al. (2008).

Data are expressed as mean ± standard deviation.
I:G, insulin:glucose ratio; BUN, blood urea nitrogen; T-Chol, total cholesterol; TG, total triglycerides; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP,
alkaline phosphate; T-Bil, total bilirubin; LDH, lactate dehydrogenase; TP, total proteins.

were greater in the NW group (2.46 ± 2.11 ng/mL) than the OB group
(1.21 ± 0.96 ng/mL; P < 0.05; Fig. 2B).
Elevated SABP values were observed in the OB group com-
pared with the NW group (P < 0.001; Fig. 3A), with hypertension
present in 9/20 OB dogs (Table 2). In the OB group, ECG revealed
19 animals with respiratory sinus arrhythmia (ASR), one dog with
sinus tachycardia and three dogs with ST segment depression
(suggestive of myocardial hypoxia). In two OB animals, enlarge-
ment of the left ventricle was detected. With the exception of one
dog with sinus bradycardia, due to vagal hypertonicity, the dogs in
the NW group showed the presence of ASR. The average electrical
axis was within the normal range in all cases and there were no
significant differences in heart rates between the two groups (OB
group 121 ± 17; NW group 111 ± 16).

Fig. 1. Box-plots representing serum concentrations of (A) tumour necrosis factor (TNF)-α and (B) interleukin (IL)-6 in normal weight (NW) and obese (OB) dogs. Medians
are represented as lines in the box-plot. The range of values is represented by whiskers and outliers are shown as black circles.
 D. Piantedosi et al. / The Veterinary Journal 216 (2016) 72–78 75

Fig. 2. Box-plots representing serum concentrations of (A) leptin and (B) adiponectin in normal weight (NW) and obese (OB) dogs. Medians are represented as lines in the
box-plot. The range of values is represented by whiskers and outliers are shown as black circles. a,bP < 0.05; c,dP < 0.01.

Five OB dogs had hyperechogenicity involving one or more zones
of the left ventricular subendocardium, suggestive of mild fibrosis
(Bonagura and Luis Fuentes, 2015). Both left ventricle free wall
(LVFWd) and interventricular septal thickness (IVSd) at end-
diastole were greater in the OB group than the NW group (P < 0.001
and P < 0.05, respectively; Table 2; Fig. 3B). Seven of 20 OB dogs had
elevated LVFWd and 1/20 OB dog had elevated IVSd values. When
compared with reference ranges based on BW, five hypertensive
OB dogs had increased LVFWd. Although pulmonary arterial
hypertension was not observed in any of the dogs, one OB dog
demonstrated an impaired ventricular relaxation type pattern of
trans-mitral flow.
Four of 20 OB dogs were categorised as having ORMD. In asso-
ciation with the increased BCS, these dogs showed high values for
glucose (one dog), total cholesterol (three dogs), triglycerides (three
dogs) and/or SABP (three dogs). These particular OB dogs also showed
elevated triglyceride values (P < 0.05) when compared with other
OB dogs. Three dogs with ORMD were also hypertensive and two
dogs demonstrated left ventricle concentric hypertrophy (LVH), one
with a symmetric pattern and one with involvement of LVFWd.

Fig. 3. Box-plots representing (A) systolic arterial blood pressure (SABP) and (B) left ventricle free wall (LVFWd) and interventricular septal thickness (IVSd) at end-diastole
in normal weight (NW) and obese (OB) dogs. Medians are represented as lines in the box-plot. The range of values is represented by whiskers and outliers are shown as
black circles. a,bP < 0.05; e,fP < 0.001.
76 D. Piantedosi et al. / The Veterinary Journal 216 (2016) 72–78

Table 2 In the present study, there were no significant differences in

Systemic blood pressure and echocardiographic findings in obese and normal weight serum TNF-α and IL-6 concentrations between OB and NW groups.
dogs.
German et al. (2009) observed a reduction in circulating TNF-α in
Parameter Unit OB group NW group P value overweight dogs enrolled in a weight loss programme, whilst no
(n = 20) (n = 20)
changes for IL-6 were reported. In contrast, a similar study did not
SABP mm/Hg 163.0 ± 25.2 131.5 ± 19.4 <0.001 show any reduction in pro-inflammatory cytokines during weight
DABP mm/Hg 89.0 ± 15.0 79.9 ± 8.8 0.051 loss (Bastien et al., 2015) and a recent study evaluating a weight
MABP mm/Hg 114.0 ± 14.0 97.1 ± 10.8 0.001
LA mm 24.4 ± 4.9 22.4 ± 3.8 0.167
gain programme in Beagle dogs did not demonstrate any changes
AO mm 19.0 ± 3.3 17.9 ± 2.9 0.051 in serum TNF-α or IL-6 concentrations (Van de Velde et al., 2013).
LA/AO ratio 1.26 ± 0.2 1.32 ± 0.1 0.355 In the present study, serum TNF-α and IL-6 were below the limit
LVIDd mm 31.4 ± 4.3 29.2 ± 7.2 0.503 of detection of the assays in several dogs in both the NW (n = 3) and
LVIDs mm 18.9 ± 3.5 18.8 ± 5.0 0.982
OB (n = 3) groups. In humans with obesity, insulin resistance is cor-
IVSd mm 7.84 ± 1.7 6.3 ± 1.0 0.019
LVFWd mm 8.3 ± 1.3 6.3 ± 1.1 <0.001 related with elevated pro-inflammatory cytokines (Hotamisligil et al.,
FS % 39.2 ± 7.5 36.8 ± 5.0 0.259 1995; Senn et al., 2002). Although there was a lack of evidence of
EF % 70.6 ± 9.9 67.8 ± 6.6 0.301 elevated cytokines in the blood of OB dogs, autocrine/paracrine reg-
EDV-I mL/m2 58.9 ± 13.9 70.1 ± 22.9 0.070 ulation of adipose tissue, mediated locally by inflammatory cytokines,
ESV-I mL/m2 17.1 ± 5.7 23.0 ± 9.3 0.059
AO-PV cm/s 131.8 ± 25.8 125.3 ± 14.6 0.334
induces insulin resistance by multiple effects on insulin signalling
PO-PV cm/s 96.2 ± 11.9 89.2 ± 14.4 0.102 (Coppack, 2001).
E-wave cm/s 64.7 ± 9.4 66.9 ± 13.5 0.564 Analysis of blood samples indicated lower circulating adiponectin
A-wave cm/s 64.1 ± 9.2 60.5 ± 10.6 0.300 concentrations in OB dogs, which might be related to insulin re-
E/A ratio 1.0 ± 0.1 1.1 ± 0.1 0.079
sistance. This particular adipokine could reduce insulin sensitivity
Data are expressed as mean ± standard deviation. through the action of AMP-activated protein kinase (Hotta et al.,
SABP, systolic arterial blood pressure; DABP, diastolic blood arterial pressure; MABP, 2001). As reported in humans (Jung et al., 2014), low adiponectin
mean blood arterial pressure; LA, left atrium; AO, aorta; LVIDd, left ventricle inter-
nal diameter at end-diastole; LVIDs, left ventricle internal diameter at end-systole;
values might be predictive of hypertension in obese dogs. Con-
IVSd, interventricular septum at end-diastole; LVFWd, left ventricle free wall at end- versely, a recent retrospective study concluded that obesity was not
diastole; FS, fractional shortening; EF, ejection fraction; EDV-I, end-diastolic volume a risk factor for systemic hypertension in dogs, instead being related
index; ESV-I, end-systolic volume index; AO-PV, aortic peak velocity; PO-PV, pul- to co-morbidities, such as chronic kidney disease, heart disease and
monary peak velocity.
endocrinopathies, although the authors did not clarify whether such
pathological conditions might be associated with obesity
(Pérez-Sánchez et al., 2015). We confirmed that plasma leptin was
Discussion elevated in obese dogs, which is consistent with previous studies
(Jeusette et al., 2005; Ishioka et al., 2007).
In this study, the metabolic panel confirmed that hyperlipidaemia LVH is a frequent complication in obese humans, with preva-
is a common serum biochemistry finding in obese dogs (Peña et al., lence estimates of up to 85% (Cuspidi et al., 2014). There are little
2008; Park et al., 2014) and revealed evidence of liver dysfunc- published data relating to cardiovascular changes associated with
tion, likely due to hepatic steatosis, as commonly reported in human obesity in dogs. The present study indicated an increased LVFWd
metabolic syndrome (Ahmed et al., 2015). There was no signifi- and IVSd in the OB group of dogs, suggesting the presence of myo-
cant difference in UP:C ratios between OB and NW groups, although cardial concentric hypertrophy; asymmetric concentric hypertrophy
the potential for renal damage could not be completely excluded without left ventricular chamber dilation was the prevalent type
in the obese dogs. Microalbuminuria has been observed in obese of cardiac remodelling observed. Similar findings have been re-
human patients with metabolic syndrome, suggesting early stage ported by Mehlman et al. (2013) in their study of obese dogs. In
renal dysfunction (Thomas et al., 2011). our study, an increase in systolic blood pressure was detected in five
The elevated serum α-globulin fraction, detected in the OB group, dogs, showing evidence of LVH. This latter finding is usually related
could be due to an increase in specific acute phase proteins, indic- to haemodynamic changes, although other factors (e.g. inflamma-
ative of an inflammatory state. Positive correlations between α-1- tory mediators, adipokines, insulin resistance, epicardial fat
antitrypsin, body mass index and waist circumference have been deposition, hyper-activation of the sympathetic and renin-
reported in human patients affected by the metabolic syndrome angiotensin-aldosterone system) have been described in obesity-
(Bogdański et al., 2006), while Swiatkowska-Stodulska et al. (2008) related left ventricle remodelling (Nadruz, 2015). In humans, diastolic
showed a positive correlation between α-2 macroglobulin and fasting dysfunction is a consequence of left ventricle remodelling. In this
insulin concentration. study, only one obese dog demonstrated an impaired ventricular
The relatively high values for fasting insulin and increase in I:G relaxation type pattern of the trans-mitral flow and the E/A ratio
ratio seen in the OB group could be related to peripheral insulin re- was unchanged in the OB group compared with the NW group,
sistance and impaired glycaemic control. This is a common feature similar to that reported by Mehlman et al. (2013).
in human obesity, which can lead to the development of type 2 di- In order to define canine ORMD, Tvarijonaviciute et al. (2012b)
abetes mellitus (Sperling et al., 2015), although there is little evidence modified the diagnostic criteria for human metabolic syndrome, as
that obesity is a primary risk factor for canine diabetes mellitus. The suggested by the International Diabetes Federation.1 In our study,
physiological and pathological mechanisms involved in the tran- four obese dogs were classified as affected by ORMD using this
sition from impaired glucose control to overt diabetes mellitus scheme; this was associated with increased insulin and decreased
are still not completely understood, although several factors adiponectin concentrations. Moreover, the presence of elevated cir-
have been proposed. In obese human patients, insulin resistance and culating triglycerides in those dogs classified as having ORMD,
impaired glucose tolerance are often associated with a chronic in- compared with the other obese dogs, is suggestive of a specific
flammatory state and an increase in plasma non-esterified fatty acids dysmetabolic syndrome. Only one OB dog showed a serum glucose
(Kruszynska et al., 1997; Shah et al., 2002; Eckel, 2005). Recently,
in an experimental study, dogs fed a high-fat diet demonstrated ev-
idence of insulin resistance, with impaired insulin release in isolated 1
International Diabetes Federation. Worldwide definition of the metabolic syn-
pancreatic islets (Woolcott et al., 2015). drome. http://www.idf.org/metabolic-syndrome (accessed 1 August 2015).
 D. Piantedosi et al. / The Veterinary Journal 216 (2016) 72–78
concentration above the upper limit for ORMD, although this finding
could be due to the small number of dogs with this specific met-
abolic dysfunction. It might be useful to investigate other parameters,
such as fructosamine or glycated haemoglobin (HbA1c) to better
assess glycaemic control, as described in humans (Martini et al.,
2015). The presence of ORMD does not seem to be associated with
total fat mass, as measured by dual-energy X-ray absorptiometry
(DXA), suggesting that other factors (such as diet) can influence de-
velopment of metabolic dysfunction in obese dogs (Tvarijonaviciute
et al., 2012b). One limitation of the current study was the variabil-
ity of the diet, in terms of the amount and type of food provided,
since they were client-owned dogs. Furthermore, the metabolic
profile observed may also be influenced by the duration of obesity,
which was not necessarily easy to establish accurately, on the basis
of the information provided by the dog’s owners.
Conclusions
The findings of this study indicate that there are metabolic dis-
turbances in obese dogs, including hyperlipidaemia associated with
the presence of liver dysfunction, compared to non-obese dogs.
However, there was no evidence of a low-grade chronic inflamma-
tory state in the obese dogs tested (as determined by measuring
circulating TNF-α and IL-6), which is different to that observed in
obese humans. Obesity in dogs can be associated with systemic hy-
pertension and LVH; a thorough cardiovascular assessment should
be considered as part of the clinical examination of an obese dog.
Our study highlights that application of criteria for classification of
canine ORMD can identify dogs demonstrating a dysmetabolic state,
similar to that observed in human metabolic syndrome. Such cases
demonstrate hypoadiponectinaemia, hyperinsulinaemia and insulin
resistance, which could represent a useful indicator of ORMD in obese
dogs seen in veterinary clinical practice.
Conflict of interest statement
None of the authors of this paper have a financial or personal
relationship with other people or organisations that could inap-
propriately influence or bias the content of the paper.
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